Journal
GENOMICS PROTEOMICS & BIOINFORMATICS
Volume 18, Issue 5, Pages 501-515Publisher
ELSEVIER
DOI: 10.1016/j.gpb.2020.12.003
Keywords
NK cell; ATAC-seq; Programmed differentiation; FOSL2; EGR2; Dynamic regulatory network
Categories
Funding
- National Key R&D Program of China [2017YFA0102900]
- National Natural Science Foundation of China [91640113, 91940306, 31771428, 31970858, 81330071]
- Fundamental Research Funds for the Central Universities, China [YD2070002019, WK2070000158, WK9110000141]
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Natural killer (NK) cells are essential in controlling cancer and infection. However, little is known about the dynamics of the transcriptional regulatory machinery during NK cell differentiation. In this study, we applied the assay of transposase accessible chromatin with sequencing (ATAC-seq) technique in a home-developed in vitro NK cell differentiation system. Analysis of ATAC-seq data illustrated two distinct transcription factor (TF) clusters that dynamically regulate NK cell differentiation. Moreover, two TFs from the second cluster, FOS-like 2 (FOSL2) and early growth response 2 (EGR2), were identified as novel essential TFs that control NK cell maturation and function. Knocking down either of these two TFs significantly impacted NK cell differentiation. Finally, we constructed a genome-wide transcriptional regulatory network that provides a better understanding of the regulatory dynamics during NK cell differentiation.
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